Nucleophilic Addition

• Requirements of a reaction:

  • must collide in correct orientation
  • collide with sufficient energy for a reaction to occur
• A reaction will occur when there is an energetically favourable oath by which electrons can flow from electron rich to electron deficient
• Nucleophiles have an electron pair which can be donated to an electrophile to form a chemical bond - molecules with a free pair of electrons or one pi bond can act as a nucleophile
• Three classes of nucleophiles:

  • with a non-bonding lone pair of electrons
  • organometallic reagents
  • pi bonds
• Compound with C-Metal bond are considered a nucleophile as there is an electronegativity difference so will be polarised
• Aldehydes are more reactive than ketones towards nucleophilic attacks for both steric and electronic reactions
• Aldehyde is less crowded and stable, so is more reactive
• Ketones is more crowded and stable, so is less reactive
• Nucleophilic attack at the carbonyl group with LiAlH4 as a source of H- results in the addition of H2 across the C=O pi bond which reduces the carbonyl group to an alcohol
• Aldehydes and ketones may also be reduced to a methylene group by direct deoxygenation using hydrazine and a base at high temperatures
• Oxygen nucleophiles from water has two possible mechanisms which depends on if it is an acid or base being catalysed
• Oxygen nucleophiles from alcohols from an acetal or a hemi-acetal. In this case, alcohol are considered a derivative of water as H is replaced by a C-based group
• Synthesis of acetals is reversible, so a mixture of products and stating materials are always obtained - water is produced so a dehydrated agent can be used to remove the water to force the reaction to give the acetal product
• Nitrogen nucleophiles from amines contain a non bonded electron pair on N atom which can be classified as primary, secondary or tertiary
• Reaction of an aldehyde of ketone with a primary amine produces an amine - overall reaction is the replacement of C=O with C=NR, a two step process:

  1. nucleophilic addition of the primary amine
  2. elimination of water

  Elimination is important as the reaction is driven to form the product by the loss of the water as each step is a reversible equilibrium
• Secondary amines react with an aldehyde or ketone to give an enamine with N atom bonded to a double bond - formed by the nucleophilic addition of a N nucleophile to a carbonyl group the the elimination of water which occur across two adjacent C atoms to form the new C=C pi bond
• Enamines react with alkyl halides rapidly and easily
• Imines and enamines are formed by a set of reversible reactions, so can be converted back to carbonyl compounds by hydrolysis with mild acid
• Aldehydes are oxidised to carboxylic acids (usually by Cr(VI)) to become a nucleophile